Clinical Significance of Ikaros in Systemic Lupus Erythematosus (SLE): A Systematic Literature Review

Ikaros in SLE
Vol. 19 No. 2 : 2024 (362-379)

Ramli N Ramli N
Johdi na Johdi na
Kamaruzaman l Kamaruzaman l
Mohd r Mohd r
Rajalingham S Rajalingham S
Azizan ea Azizan ea
Mohamed Said ms Mohamed Said ms
Shaharir SS Shaharir SS

Abstract
Systemic lupus erythematosus (SLE) is a multi-systemic chronic autoimmune disease. Ikaros is a family member of transcription factors, encoded by the Ikaros family zinc finger 1 (IKZF1) gene. It is important in hematopoiesis and immune system regulation as it helps in lymphoid cell differentiation. Ikaros functions in the pathogenesis and therapeutic target in SLE are well demonstrated in mice. This systematic review highlighted the clinical significance of Ikaros and IKZF1 in SLE patients via a comprehensive search using OVID, PubMed, and Cochrane databases. The following terms “SLE”, “lupus”, “Ikaros transcription factor”, “Ikaros zinc finger” and “IKZF” were searched and all of the relevant publications were scrutinised. Only human studies were included. A total of 22 relevant publications of Ikaros in SLE patients were included. IKZF1 polymorphisms were demonstrated to be significantly associated with SLE across different ethnicities of SLE. This association had led to clinical trials in SLE, using iberdomide that targets Ikaros. However, studies on the Ikaros gene expression and protein levels were found to be conflicting in SLE, which suggested clinical heterogeneity of the disease. In conclusion, further studies are needed to determine the exact effects of Ikaros and which subtypes of SLE patients will benefit from treatment.
Keywords : Autoimmune, gene, Ikaros;, lupus, protein,
Abstrak
Sistemik lupus eritematosus (SLE) adalah penyakit autoimun kronik yang melibatkan pelbagai sistem. Ikaros ialah faktor transkripsi utama yang dikodkan oleh gen Ikaros family zinc finger 1 (IKZF1). Ikaros memainkan peranan penting di dalam sistem darah (hematopoiesis) dan pengawalan sistem imun kerana ia membantu dalam pembezaan sel limfoid. Fungsi Ikaros telah ditunjukkan dengan jelas dalam model tikus dan kini terdapat data tentang peranannya dalam patogenesis dan target perawatan SLE. Ulasan sistematik ini menghuraikan perkaitan klinikal yang signifikan antara Ikaros and IKZF1 dalam pesakit SLE, melalui carian yang menyeluruh menggunakan pangkalan data OVID, PubMed dan Cochrane. Istilah “SLE”, “lupus”, “ikaros transcription factor”, “ikaros zinc finger” and “IKZF” telah digunakan bagi tujuan pencarian dan semua artikel yang relevan telah dianalisa. Hanya kajian yang melibatkan manusia dimasukkan dan berdasarkan kriteria inklusi, sebanyak 22 artikel yang berkaitan dengan Ikaros di dalam SLE telah terpilih. Polimorfisme IKZF1 telah terbukti berkaitan secara signifikan dengan SLE yang berlatar belakang pelbagai etnik. Hubungan ini telah mencetuskan beberapa kajian klinikal dalam SLE, menggunakan iberdromide yang bertindak terhadap Ikaros. Walau bagaimanapun, kajian tentang ekspresi gen Ikaros dan paras protein didapati tidak konsisten, dan ini kemungkinan disebabkan oleh kepelbagaian ciri klinikal penyakit SLE ini. Kesimpulannya, walaupun Ikaros berpotensi menjadi protein target rawatan di dalam SLE, kajian selanjutnya diperlukan bagi mengenalpasti kesan sebenar Ikaros, serta subset pesakit SLE yang mungkin mempunyai respon yang baik terhadap rawatan tersebut.
Kata Kunci : Autoimun, gen, Ikaros, lupus, protein,

Correspondance Address
Syahrul Sazliyana Shaharir. Rheumatology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +603-8921 5555 Email: sazliyana@ukm.edu.my


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